Interleukin-7-dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes.
CD40 antigens
autoimmunity
interleukin-7
monocytes
type 1 diabetes
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
13
08
2021
received:
22
02
2021
accepted:
04
10
2021
pubmed:
10
10
2021
medline:
10
2
2022
entrez:
9
10
2021
Statut:
ppublish
Résumé
The important role of IL-7 in the generation of self-reactive T-cells in autoimmune diseases is well established. Recent studies on autoimmunity-associated genetic polymorphisms indicated that differential IL-7 receptor (IL-7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL-7-mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL-7-mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t-distributed Stochastic Neighbor-Embedded (t-SNE)-analyses. IL-7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL-7, we detected lower monocyte IL-7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL-7 stimulation. t-SNE analyses revealed IL-7-dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA-DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL-7 and CD40/IL-7R co-expression differed between patients and controls. This study shows the unique effects of IL-7 on monocyte phenotype and functions. Lower IL-7R expression on IL-7-induced CD40
Identifiants
pubmed: 34625948
doi: 10.1002/eji.202149229
doi:
Substances chimiques
CD40 Antigens
0
IL7 protein, human
0
IL7R protein, human
0
Interleukin-7
0
Interleukin-7 Receptor alpha Subunit
0
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3214-3227Informations de copyright
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
Références
Dooms, H., Interleukin-7: fuel for the autoimmune attack. J. Autoimmun. 2013. 45: 40-48.
Calzascia, T., Pellegrini, M., Lin, A., Garza, K. M., Elford, A. R., Shahinian, A., Ohashi, P. S. et al., CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 2008. 105: 2999-3004.
Penaranda, C., Kuswanto, W., Hofmann, J., Kenefeck, R., Narendran, P., Walker, L. S., Bluestone, J. A. et al., IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells. Proc. Natl. Acad. Sci. U. S. A. 2012. 109: 12668-12673.
Mazzucchelli, R. and Durum, S. K., Interleukin-7 receptor expression: intelligent design. Nat. Rev. Immunol. 2007. 7: 144-154.
Gregory, S. G., Schmidt, S., Seth, P., Oksenberg, J. R., Hart, J., Prokop, A., Caillier, S. J. et al., Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 2007. 39: 1083-1091.
Todd, J. A., Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R. et al., Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet. 2007. 39: 857-864.
Lundtoft, C., Seyfarth, J. and Jacobsen, M., IL7RA genetic variants differentially affect IL-7Ralpha expression and alternative splicing: a role in autoimmune and infectious diseases? Genes Immun. 2020. 21: 83-90.
Lundstrom, W., Highfill, S., Walsh, S. T., Beq, S., Morse, E., Kockum, I., Alfredsson, L. et al., Soluble IL7Ralpha potentiates IL-7 bioactivity and promotes autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 2013. 110: E1761-70.
Seyfarth, J., Lundtoft, C., Fortsch, K., Ahlert, H., Rosenbauer, J., Baechle, C., Roden, M. et al., Interleukin-7 receptor alpha-chain haplotypes differentially affect soluble IL-7 receptor and IL-7 serum concentrations in children with type 1 diabetes. Pediatr. Diabetes 2018. 19: 955-962.
Lundtoft, C., Seyfarth, J., Oberstrass, S., Rosenbauer, J., Baechle, C., Roden, M., Holl, R. W. et al., Autoimmunity risk- and protection-associated IL7RA genetic variants differentially affect soluble and membrane IL-7Ralpha expression. J. Autoimmun. 2018.
Jager, J., Schulze, C., Rosner, S. and Martin, R., IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis. Genes Immun. 2013;14: 453-461.
Al-Mossawi, H., Yager, N., Taylor, C. A., Lau, E., Danielli, S., de Wit, J., Gilchrist, J. et al., Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele. Nat. Commun. 2019. 10: 4575.
Unanue, E. R., Antigen presentation in the autoimmune diabetes of the NOD mouse. Annu. Rev. Immunol. 2014. 32: 579-608.
Calderon, B., Carrero, J. A., Miller, M. J. and Unanue, E. R., Cellular and molecular events in the localization of diabetogenic T cells to islets of Langerhans. PNAS 2011. 108: 1561-1566.
Calderon, B., Carrero, J. A., Ferris, S. T., Sojka, D. K., Moore, L., Epelman, S., Murphy, K. M. et al., The pancreas anatomy conditions the origin and properties of resident macrophages. J. Exp. Med. 2015. 212: 1497-1512.
Ferris, S. T., Carrero, J. A. and Unanue, E. R., Antigen presentation events during the initiation of autoimmune diabetes in the NOD mouse. J. Autoimmun. 2016. 71: 19-25.
Bradshaw, E. M., Raddassi, K., Elyaman, W., Orban, T., Gottlieb, P. A., Kent, S. C., Hafler, D. A. et al., Monocytes from patients with type 1 diabetes spontaneously secrete proinflammatory cytokines inducing Th17 cells. J. Immunol. 2009. 183: 4432-4439.
Kallionpaa, H., Elo, L. L., Laajala, E., Mykkanen, J., Ricano-Ponce, I., Vaarma, M., Laajala, T. D. et al., Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility. Diabetes 2014. 63: 2402-2414.
Rodrigues, K. B., Dufort, M. J., Llibre, A., Speake, C., Rahman, M. J., Bondet, V., Quiel, J. et al., Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes. Diabetologia 2020.
Litherland, S. A., Xie, X. T., Hutson, A. D., Wasserfall, C., Whittaker, D. S., She, J. X., Hofig, A. et al., Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus. J. Clin. Invest. 1999. 104: 515-523.
Foss-Freitas, M. C., Foss, N. T., Donadi, E. A. and Foss, M. C., In vitro TNF-alpha and IL-6 production by adherent peripheral blood mononuclear cells obtained from type 1 and type 2 diabetic patients evaluated according to the metabolic control. Ann. N. Y. Acad. Sci. 2006. 1079: 177-180.
Devaraj, S., Glaser, N., Griffen, S., Wang-Polagruto, J., Miguelino, E. and Jialal, I., Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 2006. 55: 774-779.
Rumore-Maton, B., Elf, J., Belkin, N., Stutevoss, B., Seydel, F., Garrigan, E. and Litherland, S. A., M-CSF and GM-CSF regulation of STAT5 activation and DNA binding in myeloid cell differentiation is disrupted in nonobese diabetic mice. Clin. Dev. Immunol. 2008. 2008: 769795.
Garrigan, E., Belkin, N. S., Alexander, J. J., Han, Z., Seydel, F., Carter, J., Atkinson, M. et al., Persistent STAT5 phosphorylation and epigenetic dysregulation of GM-CSF and PGS2/COX2 expression in Type 1 diabetic human monocytes. PLoS One 2013. 8: e76919.
Borrow, P., Tishon, A., Lee, S., Xu, J., Grewal, I. S., Oldstone, M. B. and Flavell, R. A., CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response. J. Exp. Med. 1996. 183: 2129-2142.
Grewal, I. S., Xu, J. and Flavell, R. A., Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand. Nature 1995. 378: 617-620.
Price, J. D., Beauchamp, N. M., Rahir, G., Zhao, Y., Rieger, C. C., Lau-Kilby, A. W. and Tarbell, K. V., CD8+ dendritic cell-mediated tolerance of autoreactive CD4+ T cells is deficient in NOD mice and can be corrected by blocking CD40L. J. Leukoc. Biol. 2014. 95: 325-336.
Varricchi, G., Pecoraro, A., Marone, G., Criscuolo, G., Spadaro, G., Genovese, A. and Marone, G., Thymic stromal lymphopoietin isoforms, inflammatory disorders, and cancer. Front. Immunol. 2018. 9: 1595.
Alderson, M. R., Tough, T. W., Ziegler, S. F. and Grabstein, K. H., Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J. Exp. Med. 1991. 173: 923-930.
Gessner, A., Vieth, M., Will, A., Schroppel, K. and Rollinghoff, M., Interleukin-7 enhances antimicrobial activity against Leishmania major in murine macrophages. Infect. Immun. 1993. 61: 4008-4012.
Tantawichien, T., Young, L. S. and Bermudez, L. E., Interleukin-7 induces anti-Mycobacterium avium activity in human monocyte-derived macrophages. J. Infect. Dis. 1996. 174: 574-582.
Leung, G. A., Cool, T., Valencia, C. H., Worthington, A., Beaudin, A. E. and Forsberg, E. C., The lymphoid-associated interleukin 7 receptor (IL7R) regulates tissue-resident macrophage development. Development 2019. 146.
Hartgring, S. A., Bijlsma, J. W., Lafeber, F. P. and van Roon, J. A., Interleukin-7 induced immunopathology in arthritis. Ann. Rheum. Dis. 2006;65: iii69-74.
Devaraj, S., Dasu, M. R., Rockwood, J., Winter, W., Griffen, S. C. and Jialal, I., Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state. J. Clin. Endocrinol. Metab. 2008. 93: 578-583.
Giulietti, A., Stoffels, K., Decallonne, B., Overbergh, L. and Mathieu, C., Monocytic expression behavior of cytokines in diabetic patients upon inflammatory stimulation. Ann. N. Y. Acad. Sci. 2004. 1037: 74-78.
Lundstrom, W., Fewkes, N. M. and Mackall, C. L., IL-7 in human health and disease. Semin. Immunol. 2012. 24: 218-224.
Vignali, D. and Monti, P., Targeting homeostatic T cell proliferation to control beta-cell autoimmunity. Curr. Diab. Rep. 2016. 16: 40.
Fujii, S., Liu, K., Smith, C., Bonito, A. J. and Steinman, R. M., The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J. Exp. Med. 2004. 199: 1607-1618.
Hernandez, M. G., Shen, L. and Rock, K. L., CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell help. J. Immunol. 2008. 180: 4382-4390.
Carreno, B. M., Becker-Hapak, M. and Linette, G. P., CD40 regulates human dendritic cell-derived IL-7 production that, in turn, contributes to CD8(+) T-cell antigen-specific expansion. Immunol. Cell Biol. 2009. 87: 167-177.
Harnaha, J., Machen, J., Wright, M., Lakomy, R., Styche, A., Trucco, M., Makaroun, S. et al., Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells. Diabetes 2006. 55: 158-170.
Cipollone, F., Chiarelli, F., Davi, G., Ferri, C., Desideri, G., Fazia, M., Iezzi, A. et al., Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control. Diabetologia 2005. 48: 1216-1224.
Waid, D. M., Wagner, R. J., Putnam, A., Vaitaitis, G. M., Pennock, N. D., Calverley, D. C., Gottlieb, P. et al., A unique T cell subset described as CD4loCD40+ T cells (TCD40) in human type 1 diabetes. Clin. Immunol. 2007. 124: 138-148.
Wagner D. H., Jr., Overlooked mechanisms in type 1 diabetes etiology: how unique costimulatory molecules contribute to diabetogenesis. Front. Endocrinol. 2017. 8: 208.
Adankwah, E., Harelimana, J. D., Minadzi, D., Aniagyei, W., Abass, M. K., Batsa Debrah, L., Owusu, D. O. et al., Lower IL-7 receptor expression of monocytes impairs antimycobacterial effector functions in patients with tuberculosis. J. Immunol. 2021. 206: 2430-2440.
van Roon, J. A., Verweij, M. C., Wijk, M. W., Jacobs, K. M., Bijlsma, J. W. and Lafeber, F. P., Increased intraarticular interleukin-7 in rheumatoid arthritis patients stimulates cell contact-dependent activation of CD4(+) T cells and macrophages. Arthritis Rheum. 2005. 52: 1700-1710.
Li, L., Masucci, M. G. and Levitsky, V., Effect of interleukin-7 on the in vitro development and maturation of monocyte derived human dendritic cells. Scand. J. Immunol. 2000. 51: 361-371.
Cossarizza, A., Chang, H. D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W. et al., Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 2019. 49: 1457-1973.
Mair, F., Hartmann, F. J., Mrdjen, D., Tosevski, V., Krieg, C. and Becher, B., The end of gating? An introduction to automated analysis of high dimensional cytometry data. Eur. J. Immunol. 2016. 46: 34-43.
Lundtoft, C., Afum-Adjei Awuah, A., Rimpler, J., Harling, K., Nausch, N., Kohns, M., Adankwah, E. et al., Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis. PLoS Pathog. 2017. 13: e1006425.